Molecular Basis of Langerhans and Non-Langerhans Cell Histiocytic Neoplasms and Castleman Disease

Exploratory Analysis of the Molecular Basis of Langerhans and Non-Langerhans Cell Histiocytic Neoplasms and Castleman Disease

The purpose of this study is to use agnostic genomic evaluation using whole exome sequencing (WES) of a variety of rare hematologic diseases grouped under rare blood diseases and its variants to further elucidate the understanding of the chemistry of these disorders and identify potential actionable mutations that can be targeted with therapies in the context of clinical trials.

Study Overview

• Status: Suspended
• Conditions: Non-Langerhans-Cell Histiocytosis; Langerhans Cell Histiocytosis (LCH); Castleman's Disease (CD)
• Intervention / Treatment: Diagnostic test: Genetic testing

Detailed Description

The study team will examine genetic changes, also known as mutations, in the DNA of participants' blood, or if applicable, bone marrow specimen. These types of tests are increasingly used by doctors to improve the accuracy of diagnosis and make decisions during care. This study seeks to understand how many patients will benefit from this testing, and in what ways. The results of this portion of the study are placed in the individual's medical record and are communicated back to each participant.

• Study Type: Interventional
• Enrollment (Estimated): 135
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sudipto Mukherjee, MD, PhD; Phone Number: 1-866-223-8100; Email: TaussigResearch@ccf.org

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44106-5065
      • Cleveland Clinic, Case Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Must have histopathologic confirmation of the particular rare hematologic disease.

• Diseases that will be considered as rare hematologic diseases for this study will include the following

  • Langerhans cell histiocytosis (LCH)
  • Erdhiem Chester disease (ECD)
  • Rosai-Dorfman disease (RDD)
  • Miscellaneous histiocytic entities -indeterminate dendritic cell tumor, interdigitating dendritic cell sarcoma, follicular dendritic cell sarcoma, fibroblastic reticular cell tumor
  • Unicentric Castleman disease
  • Multicentric Castleman disease including TAFRO
  • Follicular Dendritic Cell sarcoma (FDCS)
• Newly diagnosed treatment naïve patients as well as patients who received prior therapies (e.g. chemotherapy, targeted therapy, surgery, or radiation) will be included. -Tissue specimens collected within the past 5 yearse will be considered acceptable for study inclusion will include the following
• Collected as part of the evaluation for diagnostic confirmation
• Tissue specimen or extracted DNA (from blood sample) banked in IRB approved tissue repositories and obtained within five years prior to the date of informed consent. -Tissue samples are planned to be collectedfrom previously stored surgical specimens already being stored in pathology lab
• Consent to have germline testing performed in parallel to tumor testingg)Patients willing to receive treatmen

Exclusion Criteria:

• Life expectancy of less than 6months
• Patient unwilling to have germline testing performed on peripheral blood or buccal mucosa

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Genomic analysis; When a participant's disorder was diagnosed, blood or tissue specimen was collected. A part of the tissue or blood will be sent to an outside company, Tempus, to be tested for specific genetic changes and the results will be sent back to participants' physician.	Diagnostic test: Genetic testing; Genetic testing of blood or tissue sample and limited medical information sent to an outside company. Database will link genome sequence data with human trait information, including cancer and other diseases, to be sent to participant's physician.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of genomic analyses yielding genetic aberrations	Proportion of genomic analyses yielding actionable genetic aberrations. "Actionable" is defined as a mutation linked to an approved therapy in the particular disease under study or another disease, a known or suspected contraindication to a given therapy, or a clinical trial linked to the alteration	Up to 12 months from last participant accrued

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of genomic analyses yielding actionable genetic aberrations	Actionable will be defined as a mutation linked to an approved therapy in the particular disease or another disease, a known or suspected contraindication to a given therapy, or a clinical trial linked to the alteration.	Up to 12 months from last participant accrued
Proportion of genomic analyses yielding germline genetic aberrations		Up to 12 months from last participant accrued
Referral rates for genetic counseling for germline mutations	Number of participants with germline mutations who were referred to genetic counseling through Cancer Genetics for their identified germline mutations	Up to 12 months from last participant accrued
Completion rates of genetic counseling for germline mutations	Number of participants with germline mutations who were referred to, and underwent (completed) genetic counseling through Cancer Genetics.	Up to 12 months from last participant accrued

Collaborators and Investigators

• Sponsor: Case Comprehensive Cancer Center
• Investigators: Principal Investigator: Sudipto Mukherjee, MD, PhD, Cleveland Clinic, Case Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): June 18, 2021
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): January 1, 2025

Study Registration Dates

• First Submitted: August 25, 2021
• First Submitted That Met QC Criteria: August 25, 2021
• First Posted (Actual): August 31, 2021

Study Record Updates

• Last Update Posted (Actual): March 22, 2024
• Last Update Submitted That Met QC Criteria: March 21, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lung Diseases; Lung Diseases, Interstitial; Neoplasms; Castleman Disease; Histiocytosis, Langerhans-Cell; Histiocytosis; Histiocytosis, Non-Langerhans-Cell
• Other Study ID Numbers: CASE7Z20

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Deidentified IPD will be shared to maintain patient confidentiality

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes